Risk Assessment of Esophageal Adenocarcinoma Using γ-H2AX Assay

Abstract Background: Mutagen-induced DNA damage as measured in peripheral blood lymphocytes (PBL) has been associated with increased risks of cancers. The formation of γ-H2AX is an early cellular response to DNA double-strand breaks (DSB). We hypothesize that higher level of radiation-induced γ-H2AX in PBLs may be associated with an increased risk of esophageal adenocarcinoma. Methods: Laser scanning cytometer-based immunocytochemical method was used to measure baseline and irradiation-induced γ-H2AX levels in PBLs from 211 patients with esophageal adenocarcinoma and 211 healthy controls. The ratio of induced γ-H2AX level to baseline level was used to evaluate individual susceptibility to DSBs. Relative risks for esophageal adenocarcinoma associated with γ-H2AX were assessed by multivariable logistic regression analysis. Results: Radiation-induced γ-H2AX level and the γ-H2AX ratio were significantly higher in cases than in controls. Dichotomized at the median in controls, a significantly increased risk for esophageal adenocarcinoma was observed in association with high γ-H2AX ratio [OR = 2.94; 95% confidence interval (CI), 1.83–4.72]. Quartile analyses showed significant dose–response associations between higher γ-H2AX ratio and increased risk of esophageal adenocarcinoma (Ptrend, 1.64E-06). In addition, joint effect between γ-H2AX ratio and smoking was observed: smokers who had high γ-H2AX ratio exhibited the highest risk of esophageal adenocarcinoma (OR = 5.53; 95% CI, 2.71–11.25) compared with never smokers with low γ-H2AX ratio. Conclusion: Radiation-induced DNA damage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. Impact: γ-H2AX assay is a new and robust method to measure DSB damage in PBLs, which can be used to assess mutagen sensitivity and esophageal adenocarcinoma risk. Cancer Epidemiol Biomarkers Prev; 22(10); 1797–804. ©2013 AACR.